At Queen Mary University in London, researchers have conducted the largest study of genetic sequencing of human diseases known to date, identifying the genetic basis of six different diseases: autoimmune thyroid disease, celiac disease, Crohn’s disease, psoriasis, multiple sclerosis, and type 1 diabetes. For these diseases, the exact cause is not known, but according to the study, it was believed that the diseases were a complex combination of both genetic and environmental factors. For each disease, there was only a small portion of hereditability is explained by genetic variants.
In past studies and experiments, genetic variants were only identified as weak-effect. For this study, global scientists used highly throughput sequencing techniques in order to identify new variants, along with rarer and higher risk variants. In a previous experiment that contained twenty-five risk genes, the risk genes were found in a sample of nearly 42,000 individuals, 24,892 of the individuals with autoimmune disease, and 17,019 individuals were controls.
Within the May 2013 edition of the journal Nature, scientists suggest that the overall genetic risk of these diseases more than likely involves a complex combination of weak-effect variants which are common in the overall human population. David van Heel, Professor of Gastrointestinal Genetics at Barts and Queen Mary University, led the study, saying that there is a lesser risk of autoimmune disease from a few high-risk genetic variations, and a greater risk of random selection from the common genetic variants, each having a weak effect. Heel goes on to say that the genetic risk likely comes from inheriting a large amount of common variants from both parents. This would mean that it would be nearly impossible to test individually for such diseases. However, scientists are started to grasp the biological basis for the conditions that cause these diseases, opening a pathway for researchers to follow, hopefully leading to new drug avenues and possible treatment options.
By Lauren Horne
Queen Mary, University of London (2013, May 22). Largest genetic sequencing study of human disease. ScienceDaily. Retrieved May 23, 2013,
A new study by researchers at the Albert Einstein School of Medicine dramatically underscores the potential role of the NF-kB protein in aging. NF-kB is a master protein which controls many inflammatory chemicals throughout the body. Researchers at the Roskamp Institute have studied NF-kB for many years as a potential way of controlling chronic inflammation which accompanies aging and underlies conditions such as Alzheimer’s disease. This new study points to a part of the brain as regulating the aging process. The current view of aging generally suggests that enzymes, DNA, proteins and other constituents of the body essentially “wear out” with age, accumulating damage due to environmental insults until they no longer function properly. This new study suggests something quite different, namely that a part of the brain called the Hypothalamus deliberately induces aging throughout the body. It has been suggested that one reason why the brain might take such drastic action is to inhibit reproduction past a certain age. This suggestion is highly speculative at this stage, but the data offered by the Albert Einstein researchers suggests that, with age, increased NF-kB activity triggers degeneration in both the brain and other areas of the body. The researchers showed that as mice aged, they increasingly expressed NF-kB in the part of the brain that is normally responsible for the production of reproductive and growth hormones. The researchers artificially manipulated NF-kB activity using genetic techniques and showed that reducing NF-kB activity was associated with better performance in cognitive tests, greater muscle strength and greater bone mass and skin thickness. Conversely, exacerbation of NF-kB activity increased all of these peripheral signs of aging, as well as reducing cognitive abilities. Furthermore the research suggested that microglia (the inflammatory cells resident in the brain) are the originators of the NF-kB activity and this spreads to nearby neurons, including those responsible for growth and reproductive hormones. These findings are of direct significance to work at the Roskamp Institute as researchers there have shown that increased NF-kB collates strongly with Alzheimer’s pathology and pathology of other central nervous system disorders. Moreover, they have worked extensively on ways to reduce NF-kB activation, particularly using the naturally occurring compound Anatabine. Roskamp Institute researchers have shown in multiple preclinical studies of neuroinflammation (such as Alzheimer's, traumatic brain injury and Multiple Sclerosis) that Anatabine (supplied by RockCreek Pharmaceuticals) has potent anti-inflammatory properties. This new finding suggests that NFKB inhibitors might also have a role in decelerating aging. In fact, preliminary studies at the Roskamp Institute suggest that mortality in mice with Alzheimer pathology is reduced by Anatabine treatment. Additional studies are needed to clarify whether Anatabine might reduce the Hypothalamic inflammation and increase the release of hormones that oppose aging.
Dr. Michael Mullan M.D., Ph.D
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